Abstract
GABA mimetics and possibly GABA have several sites of action in the central nervous system: (a) the extrapyramidal(as well as limbic) DA neurons are inhibited by GABA mimetics(e.g. SL 76002) resulting in decreased DA turnover and potentiation of neuropleptic-induced catalepsy; (b) striatal cholinergic (inter)neuron activity is reduced by enhanced GABA-ergic transmission: this results in facilitation of striatal control of motility and muscle tone as evidenced by the potentiation of apomorphine-induced stereotypies and antagonism of neuroleptic-induced catalepsy. The cholinergic system is sensitive to very low doses of GABA mimetics; (c) a (striatal) system postsynaptic to both DA and ACh neurons is involved in the changes in striatal function subsequent to sustained blockade of dopaminergic transmission: thus, GABA mimetics prevent the tolerance to the cataleptogenic action of neuroleptics and the development of supersensitivity to apomorphine; (d) limbic noradrenergic neuron activity is enhanced by GABA mimetics. The therapeutic implications of these findings with GABA mimetics lie in extrapyramidal (Huntington's chorea, neuroleptic-and L-DOPA-induced dyskinesias) and limbic (schizophrenia, depression) disorders; also, epilepsy and spasticity have to be considered.
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